Investigating the role of GLI2 in B cells 2961

Description To recognize and clear an antigen, B cells undergo activation, differentiation, maturation and class switch recombination. The glioma-associated protein-2 (GLI2) transcription factor has been identified as a regulator of IgM secretion in Waldenström macroglobulinemia, a B cell lymphoma characterized by the overproduction of IgM. However, the role of GLI2 in IgM secretion by normal B cells has not been investigated. We generated mice with conditional Gli2 deletion in hematopoietic cells (H-Gli2-/-) by crossing Gli2fl/fl and Vav-icre+/- mice. Cells from the bone marrow, spleen, peripheral blood (and thymus) of the H-Gli2-/- and wild-type mice were analyzed by flow cytometry to determine phenotypic differences in lymphocyte populations. B cell development in the bone marrow is unaltered by the lack of Gli2, while in the spleen of the H-Gli2-/- mice there are fewer marginal zone—and more follicular—B cells. Serum levels of IgM are also lower in H-Gli2-/- mice. These data show that Gli2 modulates IgM levels in normal B cells and appears to be important for later stages of B cell development. Interestingly, peripheral blood CD8+ T cells are lower in the H-Gli2-/- mice, despite similar numbers present in the thymus, suggesting Gli2 modulates peripheral CD8+ T cell proliferation/survival. These findings will inform further studies of the molecular mechanisms by which GLI2 modulates antibody production and its potential role in B and T cell functions in normal and disease states.